Can Obsessive-Compulsive Disorder Be Blocked in the Brain?

In OCD a thought that repeats again and again—“my hands are dirty, my hands are dirty”—can recur in a habitual way. Such conditions occur in people from different countries and cultures, suggesting that they represent a core dysfunction related to an imbalance between behaviors.

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For children and adults who have conditions such as obsessive-compulsive disorder (OCD), Tourette syndrome or autism, repetitive thoughts and actions can occur even if the individuals do not want them to. In OCD a thought that repeats again and again—“my hands are dirty, my hands are dirty”—can recur in a habitual way. Such conditions occur in people from different countries and cultures, suggesting that they represent a core dysfunction related to an imbalance between behaviors. These problems appear to reflect disturbances in brain circuits that are different from, but allied with, the normal habit circuits.

Researchers in our group and that of Susanne Ahmari at the University of Pittsburgh have tested whether these OCD circuits can be controlled. Our lab group stimulated the neocortex and striatum in mice that were genetically engineered to have OCD-like traits. These mice groom themselves excessively, especially around the face. In the lab we mimicked a problem that people with OCD often have because they react excessively and repetitively to some trigger stimulus in the environment. We conditioned the mice to learn that after a tone sounded a drop of water would fall on their noses about a second later. We also performed the same routine with normal (“control”) mice. The OCD-like mice started by just grooming when the water drop came, but then began to start grooming in response to the tone alone, and kept grooming all the way through when the drop fell. The control mice learned to suppress this early grooming, which after all was a wasted effort because the water drop came later. The OCD-like mice groomed compulsively every time the external cue sounded.

Using optogenetics—a technique that controls the activity of brain cells by shining light on them—we then excited a pathway that connects a small region in the cortex with the striatum. The pathway has been implicated in suppressing behaviors. This treatment immediately blocked the compulsive early grooming in the mutant mice! Yet when the water drop came, they could groom normally. And the optogenetic stimulation did not affect other normal behaviors such as eating; it selectively blocked the compulsive aspect of behavior.

These results provide tantalizing evidence that compulsive behaviors depend on pathways interconnecting the neocortex and striatum, just as entrenched habits do. Moreover, Ahmari’s group has found that stimulation of a nearby part of the neocortex can actually induce repetitive behaviors that resemble those in OCD. These studies suggest that in the future therapies may be developed that could help people with such disorders.

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ABOUT THE AUTHOR(S)

Ann Graybiel is an institute professor at the Massachusetts Institute of Technology and an investigator at the McGovern Institute for Brain Research at M.I.T. Kyle Smith is an assistant professor of psychological and brain sciences at Dartmouth College. The M.I.T. portion of the research described here was conducted by Eric Burguière.